Our long-term goal is the elucidation of the neurochemical substrates and neural loci involved in the control of male sexual behavior. Androgens are necessary, but not sufficient, for normal sexual behavior. Previous studies indicate a role for adrenergic transmitters and neuropeptide Y, and have demonstrated the importance of the medial preoptic area in the regulation of male sexual behavior. An important task is the identification of the molecular substrates mediating the effects of androgens on male sexual behavior. We suggest that molecular changes in neurons synthesizing and secreting (presynaptic) adrenergic transmitters and neuropeptide Y (which are often colocalized), and in neurons responding to these chemical messengers (postsynaptic) are modified by androgen exposure. These modifications may underlie the behavioral effects of androgens on sexual function. To test this hypothesis we will examine castration-induced changes in gene expression for neuropeptide Y in relevant brain regions projecting to the medial preoptic area - the hypothalamic arcuate nucleus and the cell groups of the brainstem that synthesize adrenergic transmitters and neuropeptide Y. Additionally, gene expression of alpha-2- adrenoceptors and NPY-Y1 receptors will be performed in the medial preoptic area. Gene expression will be quantified using ribonuclease protection (solution hybridization) assays of microdissected brain regions. Localization of changes will be performed using in situ hybridization. In addition to the media preoptic area, in situ hybridization analyses will be performed on the hypothalamic arcuate and paraventricular nuclei, and on the medal nucleus of the amygdala. Following characterization of the time-course of castration-associated changes in gene expression, we will evaluate the effects of androgen replacement therapy. We predict that castration will be associated with decreases in neuropeptide Y gene expression within the hypothalamic arcuate nucleus, but not in the brainstem. Further, the decrease in gene expression will not be evident until 2-4 weeks after castration, and will be accompanied by increases in gene expression for the NPY-Y1 receptor, but not in gene expression for the alpha-2-adrenoceptor. The changes in receptor gene expression will be limited to the media preoptic area and hypothalamic paraventricular nucleus. Castration- induced changes will be reversed by androgen treatment in a dose- related manner. Finally, we will evaluate whether modifications in adrenergic-NPY mechanisms underlie the "progonadal" effects of sexual experience. These studies will serve as a training vehicle for a minority doctoral student The data generated will clarify how androgen- adrenergic-neuropeptide Y interactions in relation to sexual function.